PubMed Health⌕ Search

Biomedical subjects

T Shimosawa

Publications and source records attributed to T Shimosawa.

33 records · Page 2Linked to original sources
PubMed1996

Local renin-angiotensin system in sympathetic overactivity of spontaneously hypertensive rats.

The present study was designed to clarify whether modulation of norepinephrine (NE) release by vascular angiotensin (Ang) II is involved in the increased peripheral sympathetic activity of spontaneously hypertensive rats (SHR). In the perfusion system of isolated mesenteric vascular beds, periarterial nerve stimulation (PNS)-evoked NE overflow was significantly greater in SHR than Wistar-Kyoto rats (WKY). Administration of Ang II increased PNS-induced NE overflow, which could be reversed by pretreatment with the AT1 receptor antagonist CV-11974 in both types of rats; the facilitation by Ang II was more potent in SHR. Moreover, CV-11974 by itself could attenuate PNS-evoked NE overflow, the extent of which was also significantly greater in SHR, suggesting an augmented sympatho-facilitatory effect of endogenous Ang II in SHR. Consistently, sympatho-facilitation by Ang I, which could be abolished by the angiotensin converting enzyme (ACE) inhibitor imidaprilat, was apparently greater than that of Ang II in SHR, despite no difference in WKY. These findings suggest that the increased peripheral sympathetic activity in SHR is attributed not only to the elevated sensitivity of nerve endings to Ang II but also to the increased local generation of Ang II, an effect possibly mediated by augmented vascular ACE activity.

Angiotensin II↗
PubMed1995

Proadrenomedullin NH(2)-terminal 20 peptide, a new product of the adrenomedullin gene, inhibits norepinephrine overflow from nerve endings.

Proadrenomedullin NH(2)-terminal 20 peptide (PAMP) and adrenomedullin, which are derived from proadrenomedullin, exhibit remarkable hypotensive action. We investigated the effect of PAMP and adrenomedullin on peripheral sympathetic neutral transmission. Using perfused rat mesenteric arteries, PAMP (0, 1, 5, and 10 pmol/ml) decreased norepinephrine overflow by periarterial electrical nerve stimulation in a dose-dependent fashion (0.244 +/- 0.043, 0.231 +/- 0.048, 0.195 +/- 0.061 and 0.168 +/- 0.051 ng/gram tissue weigh: NS, P < 0.05, and P < 0.02, respectively). In contrast to PAMP, adrenomedullin (1, 5, and 10 pmol/ml) did not change it. In contrast, vasoconstrictive response of mesenteric arteries to exogenous norepinephrine was significantly attenuated by 10 pmol/ml of adrenomedullin but not by the same dose of PAMP. Calcitonin gene-related peptide (8-37) [CGRP(8-37)], a CGRP receptor antagonist, inhibited the vasodilatory effect of adrenomedullin but could not suppress the sympathoinhibitory effect of PAMP. Neither a nicotinic antagonist, hexamethonium, nor a presynaptic alfa2 antagonist, yohimbine, blocked the sympathoinhibitory effect of PAMP. Thus, it suggests that PAMP and adrenomedullin, which are derived from the same gene, exhibit different hypotensive mechanisms: PAMP inhibits neural transmission at peripheral sympathetic nerve ending, although adrenomedullin directly dilates vascular smooth muscle, possibly through CGRP-like receptor.

Adrenomedullin↗
PubMed1995

Effect of a calcium antagonist on renal hemodynamics in salt-loaded spontaneously hypertensive rats.

In the present study, we investigated the change in renal hemodynamics induced by a calcium antagonist in young (6 week-old) spontaneously hypertensive rats (SHR), a salt-sensitive hypertensive model. In acute experiments, SHR were fed either a 0.66% or 8.0% NaCl diet for 4 weeks. In acute experiments, manidipine, a calcium antagonist, was administered in a bolus dose of 10 microg/kg. In chronic experiments, SHR were fed a 0.66% NaCl, 0.66% NaCl plus 0.05% manidipine, 8.0% NaCl or 8.0% NaCl plus 0.05% manidipine diet for 4 weeks. Mean arterial pressure (MAP), glomerular filtration rate (GFR), and renal blood flow (RBF) were measured. Salt loading increased MAP in young SHR. Acute administration of manidipine decreased MAP more in salt-loaded SHR compared to non-salt-loaded SHR (-43.3 +/- 3.1 vs. -18.6 +/- 2.1 mmHg: p < 0.01). Moreover, chronic administration of manidipine attenuated the rise in MAP in salt-loaded SHR (155 +/- 3 mmHg vs. 196 +/- 5 mmHg; p < 0.01) and less so in non-salt-loaded SHR (150 +/-2 mmHg vs. 160 +/- 3 mmHg; p < 0.01). Salt loading elevated renal vascular resistance (RVR) but changed neither RBF nor GFR. The acute- and chronic-administration of manidipine increased RBF (Acute; +0.77 +/- 0.22 ml/min/g kidney: p < 0.05, Chronic; 4.32 +/- 0.29 vs. 5.50 +/- 0.90 ml/min/g kidney: p < 0.01) in non-salt-loaded SHR, which was greater in salt-loaded SHR (Acute; +2.19 +/- 0.52 ml/min/g kidney: p 0.05 vs. non-salt-loaded SHR, Chronic; 4.29 +/- 0.53 vs. 6.09 +/- 1.41 ml/min/g kidney: p < 0.01) Manidipine also decreased RVR (Acute; -10.2 +/- 2.2 mmHg/ml/min/g kidney: p < 0.01, Chronic; 35.3 +/- 1.6 vs. 27.3 +/- 4.1 mmHg/ml/min/g kidney: p < 0.01) in non-salt-loaded SHR, which was greater in salt-loaded SHR (Acute; -21.1 +/- 3.1 mmHg/ml/min/g kidney: p < 0.01 vs. non-salt-loaded SHR, Chronic; 44.9 +/- 2.6 vs. 27.6 +/- 4.1 mmHg/ml/min/g kidney: p < 0.01). GFR did not change significantly following manidipine. It is suggested that the antihypertensive effect of the calcium antagonist, manidipine, was greater in salt-loaded SHR and was accompanied by profound amelioration of the abnormal renal hemodynamics.

Animals↗
PubMed1993

Enhancement of vasoconstrictor response by a noncalcemic analogue of vitamin D3.

To clarify the effects of active vitamin D3 on pressor and vascular responses to vasoconstrictor substances, we studied pressor responses to the intravenous injection of norepinephrine or angiotensin II (Ang II) and vasoconstrictor responses to norepinephrine. Sprague-Dawley rats were given 1,25-dihydroxyvitamin D3 subcutaneously (200 ng/kg per day) for 14 days. The administration of 1,25-dihydroxyvitamin D3 augmented the pressor responses to norepinephrine and Ang II in conscious rats and was associated with a significant increase in serum calcium concentration (11.0 +/- 0.2 mg/dl). To further clarify whether the increased pressor response to vasoconstrictors may be due to the calcemic or direct action of active vitamin D3, we studied the effect of its noncalcemic analogue, 22-oxacalcitriol, and its inactive analogue, 24,25-dihydroxyvitamin D3, on the pressor response to vasoconstrictors in rats. The pressor responses to norepinephrine and Ang II were apparently augmented in 22-oxacalcitriol-treated rats similarly to 1,25-dihydroxyvitamin D3-treated rats. In contrast, the pressor responses were not affected by either 24,25-dihydroxyvitamin D3 or the intravenous infusion of calcium chloride. In an ex vivo experiment using a mesenteric preparation, the vascular sensitivity to norepinephrine was moderately augmented in rats treated with both 22-oxacalcitriol and 1,25-dihydroxyvitamin D3 but was not affected in rats treated with 24,25-dihydroxyvitamin D3. The results suggest that the enhanced pressor responses to norepinephrine and Ang II could be attributed to the direct effect of active vitamin D3 on vasculature rather than to hypercalcemia.

24,25-Dihydroxyvitamin D 3↗
PubMed1992

Insulin inhibits norepinephrine overflow from peripheral sympathetic nerve ending.

The effects of insulin on peripheral nervous system are unknown. We therefore studied the effects of insulin on sympathetic nerve activity in isolated mesenteric arteries of Sprague-Dawley rats. The overflow of norepinephrine (NE) by electrical stimulation was used as the index of sympathetic nervous system activity. Insulin (0.5 to 1U/l) decreased the NE release in a dose-dependent fashion. This inhibitory effect was, however, reversed by either 5 x 10(-5)M cocaine or 5 x 10(-4)M ouabain treatment. Thus, we postulate that insulin attenuates NE overflow from peripheral sympathetic nerve endings, probably due to enhanced NE reuptake.

Animals↗
PubMed1992

Diminished nocturnal decline in blood pressure in elderly hypertensive patients with left ventricular hypertrophy.

To assess the circadian blood pressure (BP) changes in elderly hypertensive patients with left ventricular hypertrophy (LVH), the ambulatory BP was measured noninvasively every 30 minutes for 24 hours in those patients with LVH (n = 15) and without LVH (n = 23), and in normotensive elderly subjects (n = 11). Although the daytime systolic BP (SBP) was comparable in the two hypertensive groups, the nighttime SBP in patients with LVH tended to be higher than in patients without LVH (149.0 +/- 15.1 versus 138.4 +/- 20.1 mm Hg, p less than 0.10). The LV mass index correlated significantly with the nighttime SBP (r = 0.43, p less than 0.01), but not with the daytime SBP (r = 0.24, ns), with clinic SBP (r = 0.14, p = ns) or the SBP after handgrip exercise (r = 0.31, p = ns). The difference in the systolic BP between daytime and nighttime (D-N SBP) in patients with LVH (2.8 +/- 9.4 mm Hg) was significantly less than that in patients without LVH (12.8 +/- 16.0 mm Hg) (p less than 0.02). In addition, the D-N SBP correlated inversely with the left ventricular mass index (r = -0.33, p less than 0.05). It was concluded that hypertension in the elderly with LVH was associated with a diminished nocturnal decline in blood pressure.

Aged↗
PubMed1992

Tumor necrosis factor-alpha induces vascular hyporesponsiveness in Sprague-Dawley rats.

The cytokine tumor necrosis factor-alpha (TNF alpha) is one of the major mediators of septic shock. Because vasodilation is a hallmark of sepsis and decreased vascular responsiveness has been implicated in the pathogenesis of septic shock, we studied the effect of TNF alpha on the mean blood pressure in conscious rats and vascular responsiveness to vasoconstrictors ex vivo using the standard organ bath method. Intravenous infusion of TNF alpha (0.006 or 0.06 mg/kg/hr for 10 hours) decreased mean blood pressure in a dose-dependent fashion. Contractile responses to norepinephrine were depressed dose-dependently in the aortic rings both with and without its endothelium. Aortic contractions by potassium depolarization were also depressed. These results suggest that TNF alpha induces non-specific vascular hyporesponsiveness, which is independent of the presence of the endothelium. The TNF alpha-induced vascular hyporesponsiveness might contribute to the hypotensive action of TNF alpha.

Analysis of Variance↗
PubMed1992

The cardiac functional reserve in elderly hypertensive patients with abnormal diurnal change in blood pressure.

OBJECTIVE: To evaluate the left ventricular function of hypertensive patients with abnormal diurnal change in blood pressure. DESIGN: We compared left ventricular structural and functional characteristics between hypertensive patients with a normal diurnal change in blood pressure (H2 group) and those with a nocturnal blood pressure increment (H1 group) using echocardiography. METHODS: The study group consisted of 36 hypertensives and 16 normotensives whose 24-h ambulatory blood pressure monitorings were measured non-invasively. The hypertensive group was subdivided into the H1 group, consisting of 11 patients (76 +/- 7 years), and the H2 group with 25 patients (73 +/- 7 years). The normotensive control group had a mean age of 73 +/- 6 years. Echocardiographic examinations were performed before and at the end of isometric exercise (handgrip for 3 min) and isoproterenol infusion (0.02 micrograms/kg per min for 5 min). RESULTS: The left ventricular mass index in the H1 group was significantly greater than in the H2 or control group. Left ventricular fractional shortening (LVFS) at rest in the H1 group was also significantly greater than in the other two groups. However, the peak late: early diastolic filling ratio, which indicated diastolic function, significantly deteriorated in the H1 group compared with the H2 and control groups. Furthermore, changes in LVFS after isometric exercise in the H1 group were more suppressed than in the H2 or control group. In addition, a significantly lower increment in LVFS after isoproterenol was observed in the H1 group compared with the H2 or control group. CONCLUSION: The H1 group had greater left ventricular mass and impaired left ventricular functional reserve than the H2 group.

Aged↗
PubMed1992

[Postprandial hypotension in the elderly with and without hypertension].

To clarify the mechanism of postprandial hypotension in the elderly, blood pressure and humoral factors were measured before and after meal, water, and glucose ingestion in 20 healthy elderly. The elderly patients were divided into 10 normotensive and 10 hypertensive cases. A reduction in systolic BP after meals in the hypertensive group was significantly larger than that in the normotensive group (-12.0 +/- 4.1 vs. 4.0 +/- 3.2 mmHg, p < 0.05). Systolic BP in hypertensive group significantly decreased at 30, 45 and 60 minutes after meals compared to the value before meals. However, no significant reduction in systolic BP was observed in the normotensive group. A change in systolic BP after meal significantly correlated with that after glucose, but not with that after water ingestion, suggesting that glucose intake mainly contributes to the postprandial hypotension in the elderly. An increase in plasma renin activity and plasma catecholamine were observed after meals in the normotensive group, but not in the hypertensive group. An increase in systolic BP significantly correlated with an increase in PRA. It was suggested that an impairment of the sympathetic nervous system in the elderly with hypertension was involved in the mechanism of postprandial hypotension.

Aged↗
PubMed1991

Effect of nifedipine tablets on ambulatory blood pressure in patients aged less than 60 and greater than 65 years with systemic hypertension.

To evaluate the effect of age on the pattern of circadian blood pressure after nifedipine tablets, ambulatory blood pressure after administration of low and high doses of nifedipine, taken twice daily, was measured over a 24-hour period in 10 elderly and 8 young hypertensive patients. After a 2-week control period without antihypertensive drug, 10 mg of nifedipine was administered twice daily for 2 weeks (low-dose period), followed by 2 weeks of 20 mg (high-dose period). At the end of each period, ambulatory BP monitoring was conducted every 30 minutes for 24 hours, using an ABPM 630 (Nippon-Colin, Komaki, Japan). In both groups, averages of systolic and diastolic BP for the entire day decreased significantly from the control to the low-dose periods. However, after the high-dose period, only the elderly group had further significant reduction of systolic BP, whereas no further reduction was seen in the young group. Separate analysis of whole-day data into daytime and nighttime values revealed that a further decrease in systolic BP after the high-dose period in the elderly group was a reflection of nighttime decline. It was suggested that circadian BP patterns after administration of nifedipine tablets in the elderly differed from those in young hypertensive patients, especially after administration of the high-dose.

Aged↗
PubMed1991

Possible role of sodium-hydrogen antiport in acetylcholine-induced relaxation of rat aorta.

The decreased extracellular Na concentration (25mM) attenuated vasodilator effect of acetylcholine (ACh) in norepinephrine-treated aortic ring. This attenuation was greater in the low Na medium substituted by Li, which can exchange intracellular H through Na-H antiport, as compared with that substituted by choline, which cannot. 10 microM amiloride canceled the difference between the two low Na mediums. Thus the inhibition of Na-H antiport may counteract the suppressive effect of decreased intracellular Na on ACh vasodilation, suggesting a possible role of Na-H antiport in a release of vasoactive substance(s) from endothelial cells.

Acetylcholine↗
PubMed1991

Antihypertensive effect of dietary calcium loading in angiotensin II-salt rats.

To clarify the hypotensive effect of high dietary Ca intake on salt-sensitive hypertension, 7-wk-old Sprague-Dawley rats, 3.15% Na and/or 4.07% Ca diet loaded, were administered 125 ng/ml of angiotensin II (ANG II) intraperitoneally for 12 days. Compared with control rats (mean blood pressure 108 +/- 2 mmHg), ANG II administration caused hypertension (131 +/- 4 mmHg, P less than 0.05). Na loading enhanced the hypertensive effect of ANG II (161 +/- 4 mmHg, P less than 0.01). Dietary Ca loading did not significantly inhibit the pressor effect of ANG II alone (119 +/- 4 mmHg). However, Ca loading suppressed hypertension in ANG II-salt rats (126 +/- 4 mmHg, P less than 0.01). Plasma total catecholamine (norepinephrine + epinephrine) was increased in ANG II-salt rats (176 +/- 14 vs. 290 +/- 23 pg/ml, P less than 0.05), but Ca loading decreased plasma catecholamine (182 +/- 13 pg/ml, P less than 0.05). In contrast, plasma catecholamine was not significantly different between ANG II-treated rats with and without Ca loading. Ca loading increased serum Ca in ANG II rats (10.9 +/- 0.1 vs. 11.7 +/- 0.1 mg/dl, P less than 0.05) but did not do so significantly in ANG II-salt rats (10.8 +/- 0.2 vs. 10.9 +/- 0.1 mg/dl). Thus Ca loading exclusively ameliorated salt-sensitive hypertension, which was induced with ANG II administration and Na loading in rats, probably through suppression of the increased sympathetic activity. In addition, these effects of Ca loading were not mediated through an increased blood level of Ca.

Angiotensin II↗
PubMedDate not supplied

Clinical effects of blood pressure biofeedback treatment on hypertension by auto-shaping.

OBJECTIVE: Although biofeedback has been reported to be efficacious in the treatment of hypertension, the degree of response has varied. This study investigated the mechanisms of blood pressure reduction by biofeedback. METHOD: Thirty outpatients with essential hypertension (10 men and 20 women) aged 38 to 65 years were studied. Subjects were randomly assigned to group A or B. Subjects in group A underwent biofeedback treatment once a week for a total of four sessions. Those in group B self-monitored their blood pressure during the sessions as the control period and later underwent the same biofeedback treatment. RESULTS: Blood pressure measured by doctor was reduced by 17 +/- 18/8 +/- 7 (p < .01) and elevation of pressure induced by mental stress testing was suppressed by 8 +/- 9 (p < .05)/4 +/- 8 during the treatment period in group A (mm Hg). In group B, both blood pressure measured by doctor and elevation of pressure by mental stress testing remained unchanged during the control period and they were later suppressed by 20 +/- 15/9 +/- 7 (p < .01) and 11 +/- 10(p < .05)/5 +/- 9 by the biofeedback treatment. Self-monitored pressure in both groups tended to decrease by the biofeedback treatment. Systolic and diastolic pressures as well as pulse rate decreased, skin temperature increased, and alpha-wave amplitude on electroencephalography increased during the therapy (p < .05). CONCLUSION: This treatment was effective in suppressing the pressor response to stress. Patients whose blood pressure increases with stress may be suited for biofeedback intervention.

Adult↗